Cardiac safety of pembrolizumab-based neoadjuvant chemoimmunotherapy in early triple-negative breast cancer: real-world experience from a single centre
P Sertic, M Trajbar, L Ledinsky, T Gaberc, L Linaric, L J Vazdar, I D GabricAbstract
Introduction
The KEYNOTE-522 study established a new standard of care for patients with high-risk early triple-negative breast cancer by introducing pembrolizumab in combination with neoadjuvant chemotherapy. Myocarditis is a known, although rare, immune-related adverse event associated with anti–PD-1 therapy, with a reported incidence of approximately 0.3–0.4% in clinical trials.
Aim
To evaluate cardiac events and treatment safety in patients treated at our University Hospital Centre.
Materials and Methods
A retrospective analysis was conducted including 45 patients with early triple-negative breast cancer who underwent surgery after completion of neoadjuvant therapy at our University Hospital Centre, between February 2024 and July 2025. Descriptive statistics were used to present demographic and clinical characteristics.
Results
The median age at diagnosis was 52 years (range 30–76). All patients were treated according to the trial protocol with pembrolizumab administered every 3 weeks in combination with chemotherapy (paclitaxel/carboplatin followed by anthracycline/cyclophosphamide), surgery, and one year of adjuvant pembrolizumab. The median number of administered anthracycline cycles was 4 (range 0–4), while the median number of pembrolizumab cycles was 17 (range 3–17). In all patients who completed the planned treatment, transthoracic echocardiography was performed either before treatment initiation or during neoadjuvant therapy prior to anthracycline administration. The median left ventricular ejection fraction (LVEF) was 64% (range 50–70%). Baseline NT-proBNP values were obtained in 76.3% of patients, while troponin I levels were measured in 64.8%.In two patients, NT-proBNP values were <8.3 ng/L; in the remaining patients, values ranged from 20 to 242 ng/L, with a median of 58.5 ng/L. Troponin I levels were <3.7 ng/L in 95.8% of patients, while one patient had a value of 11 ng/L. A total of four patients (6.6%) developed cardiac events, including atrial fibrillation with rapid ventricular response, immune-mediated myositis with severe hypothyroidism and mild pericardial effusion without LVEF impairment, and pulmonary embolism. Neoadjuvant therapy was discontinued in all cases, and patients proceeded to surgery. One additional patient developed suspected immune checkpoint inhibitor–related myocarditis after completion of neoadjuvant therapy and did not continue immunotherapy in the adjuvant setting. The median time to onset of cardiac symptoms was 4.5 months (range 2–8).
Conclusion
Our findings are consistent with limited real-world data, showing a 10–12% incidence of cardiovascular symptoms during chemo-immunotherapy and myocarditis rates comparable to clinical trials (~0.3–1.1%). The retrospective design limits the ability to attribute cardiac events solely to immunotherapy, underscoring the importance of baseline cardiovascular risk assessment and early detection of cardiotoxicity.